Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease

Journal article

Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility

Authors: Watt, S; Vasquez, L; Walter, K; Mann, AL; Kundu, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 12
• Issue: 1
• Pages: 2298-2298
• Article number: 2298
• Publication date: 2021-04-16
• DOI: 10.1038/s41467-021-22548-8
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Regulation of gene expression; Biology; Chromatin; Enhancer; Innate immune system; Cell biology; Acquired immune system; Gene; Gene expression; Immunology; Genetics; Immune system; Myeloid; Phenotype; Immunity